Evidence map›Paper›PMID 34156262›Full record

ArticlemBio2021

Neutralizing Antibodies Induced by First-Generation gp41-Stabilized HIV-1 Envelope Trimers and Nanoparticles.

Sonu Kumar, Xiaohe Lin, Timothy Ngo, Benjamin Shapero, Cindy Sou, Joel D Allen, Jeffrey Copps, Lei Zhang, Gabriel Ozorowski, Linling He and 4 more

Open access · goldAbstract read
In one paragraph

Article in mBio, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.4field-weighted citation impact, top 19% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
  2. From sequence to scaffold: Computational design of protein nanoparticle vaccines from AlphaFold2-predicted building blocks.Proceedings of the National Academy of Sciences of the United States of America · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 2 institutions in 2 countries.

Sonu Kumar *Department of Integrative Structural and Computational Biology, The Scripps Research Institutegrid.214007.0, La Jolla, California, USA.
Xiaohe Lin *Department of Integrative Structural and Computational Biology, The Scripps Research Institutegrid.214007.0, La Jolla, California, USA.
Timothy NgoDepartment of Integrative Structural and Computational Biology, The Scripps Research Institutegrid.214007.0, La Jolla, California, USA.
Benjamin ShaperoDepartment of Integrative Structural and Computational Biology, The Scripps Research Institutegrid.214007.0, La Jolla, California, USA.
Cindy SouDepartment of Integrative Structural and Computational Biology, The Scripps Research Institutegrid.214007.0, La Jolla, California, USA.
Joel D AllenSchool of Biological Sciences, University of Southamptongrid.5491.9, Southampton, United Kingdom.
Jeffrey CoppsDepartment of Integrative Structural and Computational Biology, The Scripps Research Institutegrid.214007.0, La Jolla, California, USA.
Lei ZhangDepartment of Integrative Structural and Computational Biology, The Scripps Research Institutegrid.214007.0, La Jolla, California, USA.
Gabriel OzorowskiDepartment of Integrative Structural and Computational Biology, The Scripps Research Institutegrid.214007.0, La Jolla, California, USA.
Linling HeDepartment of Integrative Structural and Computational Biology, The Scripps Research Institutegrid.214007.0, La Jolla, California, USA.
Max CrispinSchool of Biological Sciences, University of Southamptongrid.5491.9, Southampton, United Kingdom.
Andrew B WardDepartment of Integrative Structural and Computational Biology, The Scripps Research Institutegrid.214007.0, La Jolla, California, USA.
Ian A WilsonDepartment of Integrative Structural and Computational Biology, The Scripps Research Institutegrid.214007.0, La Jolla, California, USA.
Jiang ZhuDepartment of Integrative Structural and Computational Biology, The Scripps Research Institutegrid.214007.0, La Jolla, California, USA.
Scripps Research Institute · USUniversity of Southampton · GB

Funding

Identification of neutralizing epitopes on SARS-CoV-2 spike for design of vaccines and small-molecule antiviralsUM1AI144462 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI BURTON, DENNIS R. · 2019 to 2025
$201.6M
Support Component D/Vaccine Discovery, Concept to ClinicUM1AI100663 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI BURTON, DENNIS R. · 2012 to 2018
$131.5M
UC San Diego Clinical and Translational Research InstituteUL1TR001442 · NCATS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FIRESTEIN, GARY S, HOGARTH, MICHAEL · 2015 to 2024
$88.3M
VirologyP30AI036214 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI David Mitchell Smith · 1994 to 2026
$78.4M
Pushing the envelope: Optimizing vaccine display of flexibly linked HIV Env trimer immunogensP01AI124337 · NIAID · INTERNATIONAL AIDS VACCINE INITIATIVE · PI ZHU, JIANG · 2016 to 2020
$12.2M
Uncleaved prefusion-optimized trimers on nanoparticles as HIV vaccinesR01AI140844 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI ZHU, JIANG · 2019 to 2023
$4.9M
Rational design and B cell responses of HIV epitope vaccinesR01AI129698 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI ZHU, JIANG · 2017 to 2021
$3.2M
NCATS NIH HHS UL1 TR001442NIAID NIH HHS P01 AI124337NIAID NIH HHS P30 AI036214NIAID NIH HHS R01 AI129698NIAID NIH HHS R01 AI140844NIAID NIH HHS UM1 AI100663NIAID NIH HHS UM1 AI144462
6 · The paper itself

Abstract

The immunogenicity of gp41-stabilized HIV-1 BG505 envelope (Env) trimers and nanoparticles (NPs) was recently assessed in mice and rabbits. Here, we combined Env-specific B-cell sorting and repertoire sequencing to identify neutralizing antibodies (NAbs) from immunized animals. A panel of mouse NAbs was isolated from mice immunized with a 60-meric I3-01 NP presenting 20 stabilized trimers. Three mouse NAbs potently neutralized BG505.T332N by recognizing a glycan epitope centered in the C3/V4 region on BG505 Env, as revealed by electron microscopy (EM), X-ray crystallography, and epitope mapping. A set of rabbit NAbs was isolated from rabbits immunized with a soluble trimer and a 24-meric ferritin NP presenting 8 trimers. Neutralization assays against BG505.T332N variants confirmed that potent rabbit NAbs targeted previously described glycan holes on BG505 Env and accounted for a significant portion of the autologous NAb response in both the trimer and ferritin NP groups. Last, we examined NAb responses that were induced by non-BG505 Env immunogens. We determined a 3.4-Å-resolution crystal structure for the clade C transmitted/founder (T/F) Du172.17 Env with a redesigned heptad repeat 1 (HR1) bend in gp41. This clade C Env, in a soluble trimer form and in a multivalent form with 8 trimers attached to ferritin NP, and the gp41-stabilized clade A Q482-d12 Env trimer elicited distinct NAb responses in rabbits, with notable differences in neutralization breadth. Although eliciting a broad NAb response remains a major challenge, our study provides valuable information on an HIV-1 vaccine design strategy that combines gp41 stabilization and NP display.

Indexed as

AnimalsAntibodies, NeutralizingAntigens, ViralB-LymphocytesEpitope MappingEpitopesFemaleHEK293 CellsHIV AntibodiesHIV Envelope Protein gp41HumansImmunizationImmunogenicity, VaccineMiceNanoparticlesRabbitsAntibodies, NeutralizingAntigens, ViralEpitopesHIV AntibodiesHIV Envelope Protein gp41envelope trimerglycan holesgp41 stabilizationHIV-1 vaccine designnanoparticleneutralizing antibodies

Identifiers

PMID34156262
PMCPMC8262854
OpenAlexW3173602876

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.